Inside Our Cellular Invaders

When we fight an infection -- any invader -- our bodies conjure inflammatory responses, immune responses. But inside some individual cells, a similar reaction happens. Beth Knight, PhD, found out what transpires inside such cells involved in a kind of brain cancer called medulloblastoma and what role a particularly important protein plays in cancer development.
This is the second profile in a continuing series of features on UNC School of Medicine graduate students.

When Elizabeth Knight was 10 years old, her mother noticed she seemed to like to observe nature. So her mother gave her a microscope. Since then, science has been part of her life. But as she got older, she realized that she liked learning in general. “In high school, I liked most subjects, and math was probably my best. In college, though, I had a sort of epiphany that science was reality. I’ve been fascinated with studying the natural world ever since.”

Undergraduate research:

“I got the opportunity to do something called REU – research experiences for undergraduates. One summer, I did functional MRI research at the University of Minnesota. Another summer I was at Northern Arizona University looking at whether pesticides disrupt the endocrine function in bullfrogs. The field work was really fun, being in a different part of the country was great, I liked learning new lab techniques, and I enjoyed meeting new people.

Why UNC:

“I knew I wanted to go to graduate school but I wasn’t sure where or what I wanted to study. That’s a big commitment and investment. So after college, I got a job working in a lab at the Medical College of South Carolina doing research in pharmacology for two years. When I visited friends in Chapel Hill, I really liked the area. I looked into UNC and saw that it had good programs in the sciences. I moved here and worked in Steven Zeisel’s lab in nutrition for two years. I really liked the translational component of the lab; I liked the relevance of his work to disease and human health.

“I was also really interested in public health, but when I took a course I really missed the science part. So I applied to interdisciplinary biomedical science programs, and interviewed at several schools. I chose UNC because the labs just seemed to be a perfect combination of down-to-earth and friendly people, a collaborative environment, and top-notch research.”

Why the Deshmukh lab?

“The lab really fit my interests in neurobiology with relevance to human disease. Mohanish seemed like he would be a really good mentor, and he has been.

The field:

About ten years ago, a new part of the immune system called the inflammasome was discovered. Think of it like this: when you get an infection, there are different parts of the immune system that realize you’re infected. And your body responds. But at the cellular level, the cell, too, realizes it’s been invaded. Different proteins inside the cell react; they make up the inflammasome. One of the genes in the inflammasome is called ASC.

The research findings:

“I was curious whether the inflammasome operates in neurons, so I looked into this and saw that neurons did express ASC. Then I wanted to know if ASC affects a type of brain cancer called medulloblastoma. We knew that in several types of cancer ASC is not expressed. It’s silenced. So we predicted that mice that lacked ASC would become more prone to medulloblastoma tumors. But we found the opposite. If the mice didn’t have ASC, they were strikingly protected from getting cancer. We found this in two different models of mice with medulloblastoma [a type of malignant tumor found in the cerebellum of the brain.]"

The finding suggests that inhibiting ASC might possibly help treat medulloblastoma, which is more common in children. Current treatments cause serious side effects, mostly because surgery and radiation kill a lot of brain cells at a crucial time of brain development.

The future:

“I’d like to continue working on this. It’s such a new area and there’s so much to explore, so many disease states. But working on this will depend on what lab I join as a post doc. I’m looking for a good fit in a lab working in cancer biology, neurobiology, and/or immunology.

“But in the meantime I’m planning on taking a break once I finish my last paper. I plan to travel and see some friends around the country whom I haven’t been able to see for a while. I’m not sure where I’ll wind up, but I know I’ll be passionate about figuring things out and improving human health.”